Efficacy and Safety of Pentoxifylline in Improving Oxygenation in Hepatopulmonary Syndrome

NCT05373134 | Unknown

• 1 other identifier: ILBS-HPS-02
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The triad of liver disease, arterial hypoxia, and extensive pulmonary vascular dilatation is known as the hepatopulmonary syndrome (HPS). The prevalence of this syndrome ranges from 10% to 30% in people with chronic liver disease. The exact cause of HPS is unknown. Previous research has shown that eicosanoids function as vasoconstrictors and cause an increase in the number of intravascular macrophage-like cells. Cirrhosis has been linked to increased NO generation in the lungs, which has been linked to intrapulmonary venous dilation. Increased pulmonary NO production is attributed to increased expression of pulmonary vascular endothelial NO synthase (eNOS) and inducible NO synthase. Increased hepatic synthesis and release of low levels of endothelin 1 (ET-1) has been established in recent investigations to function as a trigger for increasing eNO levels. TNF (tumor necrosis factor) and ET-1 have both been linked to the onset of experimental HPS. Increased CO generation and heme oxygenase expression have been linked to the progression of HPS in recent investigations. HPS increases mortality in cirrhotic patients and may affect the frequency and severity of portal hypertension consequences. To the best of our knowledge there have been only three pilot studies in humans which checked the effect of pentoxifylline in hepatopulmonary syndrome and they showed highly contrasting results. The outcome was also measured in a short interval. Investigator hypothesize that pentoxifylline would improve the oxygenation in patients with hepatopulmonary syndrome

Conditions

Hepatopulmonary Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in AaPO2 gradient by at least 5mmHg or to a value less than 15mm Hg at the end of 6 months from baseline

  6 months

Secondary Outcomes (22)

• Change in grading of intrapulmonary shunting at the end of 3 month, from baseline as assessed by saline contrast echocardiography

  3 months

• Change in grading of intrapulmonary shunting at the end of 6 month, from baseline as assessed by saline contrast echocardiography

  6 months

• Change in DLCO (Diffusing Capacity of the lungs for Carbon Monoxide) at the end of 3 month from baseline

  3 month

• Change in Forced expiratory volume 1 (FEV1) at the end of 3 month from baseline

  3 month

• Change in FVC (Forced Vital Capacity) at the end of 3 month from baseline

  3 month

Study Arms (2)

Pentoxifylline

EXPERIMENTAL

400mg OD x 1 week, 400mg BD x 1 week then increased to 400mg TDS and continued

Drug: Pentoxifylline

Placebo

PLACEBO COMPARATOR

Placebo will be given in a same manner as experimental drug

Other: Placebo

Interventions

Pentoxifylline DRUG

400mg OD x 1 week, 400mg BD x 1 week then increased to 400mg TDS and continued

Pentoxifylline

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 - 70 years
• Evidence of portal hypertension
• Intrapulmonary vascular dilatation in the form of shunting diagnosed on contrast echocardiogram
• AaPO2 \> 15mmHg on seated room air (ABG) if age \<65years and \>20mmHg if Age≥ 70 years

You may not qualify if:

• Child C cirrhosis with CTP \> 10 or with refractory ascites
• Intrinsic significant cardiopulmonary disease
• PFT indicating severe obstructive ventilatory defect (FEV1/FVC \< 70)
• Hepatic hydrothorax, Portopulmonary hypertension
• Moderate and severe left ventricular systolic dysfunction
• Inability to perform Pulmonary function test
• Intracardiac shunting
• Current use of exogenous nitrates
• Patients already on pentoxifylline
• Prior intolerance to pentoxifylline
• Very severe cases of HPS (A-aO2 gradient ≥ 15mm Hg, PO2 \<50 mmHg)
• Active bacterial infections, active hepatic encephalopathy
• Known malignancy including HCC
• SBP on secondary prophylaxis
• CKD with creatinine clearance \< 30

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

MeSH Terms

Conditions

Hepatopulmonary Syndrome

Interventions

Pentoxifylline

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Dr Vishnu Girish, MD

CONTACT

01146300000; vishnugirish@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2022
• First Posted: May 13, 2022
• Study Start: May 5, 2022
• Primary Completion: April 30, 2023
• Study Completion: April 30, 2023
• Last Updated: May 13, 2022

Record last verified: 2022-04

Locations

IN (1)